Identification of Targetable
EGFR
Mutations in Ovarian Cancer
PURPOSE
EGFR
mutations are classically seen in non–small cell lung cancers (NSCLCs), and EGFR-directed inhibitors have changed the therapeutic landscape in patients with
EGFR
-mutated NSCLC. The real-world prevalence of
EGFR
-mutated ovarian cancers has not been previously described. We aim to determine the prevalence of pathogenic or likely pathogenic
EGFR
mutations in ovarian cancer and describe a case of
EGFR
-mutated metastatic ovarian cancer with a durable response to osimertinib, an EGFR-directed targeted therapy.
METHODS
Retrospective review of 33,850 molecularly profiled ovarian cancer samples from real-world patients who underwent next-generation sequencing (NGS) of DNA between 2016 and 2025.
EGFR
-mutated cases were defined as those harboring known pathogenic or likely pathogenic mutations based on the
EGFR
genomic alteration discovered by Caris.
RESULTS
Of 33,850 patients, 27 (0.08%) harbored a genomic alteration in the
EGFR
gene that was pathogenic or likely pathogenic, including
EGFR
exon 20 mutation (n = 12, including five patients with
EGFR
T790M mutation),
EGFR
L858R (n = 3), and an
EGFR
exon 19 deletion (n = 2). Only one patient was treated with osimertinib, a third-generation EGFR-inhibitor, and achieved a durable objective response for over 17 months.
CONCLUSION
Ovarian cancer driven by an oncogenic
EGFR
mutation is a rare occurrence, yet it is an actionable molecular target with EGFR-directed inhibitors. This underlies the potential value of comprehensive NGS in the management of ovarian cancer for discovering actionable genomic alterations.
